• 제목/요약/키워드: Effector

검색결과 840건 처리시간 0.027초

Metabolic Challenges in Anticancer CD8 T Cell Functions

  • Andrea M. Amitrano;Minsoo Kim
    • IMMUNE NETWORK
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    • 제23권1호
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    • pp.9.1-9.15
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    • 2023
  • Cancer immunotherapies continue to face numerous obstacles in the successful treatment of solid malignancies. While immunotherapy has emerged as an extremely effective treatment option for hematologic malignancies, it is largely ineffective against solid tumors due in part to metabolic challenges present in the tumor microenvironment (TME). Tumor-infiltrating CD8+ T cells face fierce competition with cancer cells for limited nutrients. The strong metabolic suppression in the TME often leads to impaired T-cell recruitment to the tumor site and hyporesponsive effector functions via T-cell exhaustion. Growing evidence suggests that mitochondria play a key role in CD8+ T-cell activation, migration, effector functions, and persistence in tumors. Therefore, targeting the mitochondrial metabolism of adoptively transferred T cells has the potential to greatly improve the effectiveness of cancer immunotherapies in treating solid malignancies.

Histone deacetylases inhibitor and RAD51 recombinase increase transcription activator-like effector nucleases-mediated homologous recombination on the bovine β-casein gene locus

  • Park, Da Som;Kim, Se Eun;Koo, Deog-Bon;Kang, Man-Jong
    • Asian-Australasian Journal of Animal Sciences
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    • 제33권6호
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    • pp.1023-1033
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    • 2020
  • Objective: The efficiency of the knock-in process is very important to successful gene editing in domestic animals. Recently, it was reported that transient loosening of the nucleosomal folding of transcriptionally inactive chromatin might have the potential to enhance homologous recombination efficiency. The objective of this study was to determine whether histone deacetylases (HDAC) inhibitor and RAD51 recombinase (RAD51) expression were associated with increased knock-in efficiency on the β-casein (bCSN2) gene locus in mammary alveolar-large T antigen (MAC-T) cells using the transcription activator-like effector nucleases (TALEN) system. Methods: MAC-T cells were treated with HDAC inhibitors, valproic acid, trichostatin A, or sodium butyrate for 24 h, then transfected with a knock-in vector, RAD51 expression vector and TALEN to target the bCSN2 gene. After 3 days of transfection, the knock-in efficiency was confirmed by polymerase chain reaction and DNA sequencing of the target site. Results: The level of HDAC 2 protein in MAC-T cells was decreased by treatment with HDAC inhibitors. The knock-in efficiency in MAC-T cells treated with HDAC inhibitors was higher than in cells not treated with inhibitors. However, the length of the homologous arm of the knock-in vector made no difference in the knock-in efficiency. Furthermore, DNA sequencing confirmed that the precision of the knock-in was more efficient in MAC-T cells treated with sodium butyrate. Conclusion: These results indicate that chromatin modification by HDAC inhibition and RAD51 expression enhanced the homologous recombination efficiency on the bCSN2 gene locus in MAC-T cells.

Targeted Editing of Myostatin Gene in Sheep by Transcription Activator-like Effector Nucleases

  • Zhao, Xinxia;Ni, Wei;Chen, Chuangfu;Sai, Wujiafu;Qiao, Jun;Sheng, Jingliang;Zhang, Hui;Li, Guozhong;Wang, Dawei;Hu, Shengwei
    • Asian-Australasian Journal of Animal Sciences
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    • 제29권3호
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    • pp.413-418
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    • 2016
  • Myostatin (MSTN) is a secreted growth factor expressed in skeletal muscle and adipose tissue that negatively regulates skeletal muscle mass. Gene knockout of MSTN can result in increasing muscle mass in sheep. The objectives were to investigate whether myostatin gene can be edited in sheep by transcription activator-like effector nucleases (TALENs) in tandem with single-stranded DNA oligonucleotides (ssODNs). We designed a pair of TALENs to target a highly conserved sequence in the coding region of the sheep MSTN gene. The activity of the TALENs was verified by using luciferase single-strand annealing reporter assay in HEK 293T cell line. Co-transfection of TALENs and ssODNs oligonucleotides induced precise gene editing of myostatin gene in sheep primary fibroblasts. MSTN gene-edited cells were successfully used as nuclear donors for generating cloned embryos. TALENs combined with ssDNA oligonucleotides provide a useful approach for precise gene modification in livestock animals.

STUDIES ON IMMUNOTOXIC POTENTIAL OF METHAMPHETAMINE (MA) IN Balb/C MICE II. The Functional Alteration of Effector Cells in Immune System

  • Lim, Chae-Woong;Rim, Byung-Moo;Lee, Ho-Il;Kim, Sang-Ho
    • Toxicological Research
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    • 제11권1호
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    • pp.15-21
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    • 1995
  • Several populations of lymphocytes possess receptors for autonomic neurotransmitter, which make lymphocytes susceptible to autonomic stimulation. This study was to evaluate the functional alternation of effector cells of the immune system. Female Balb/C mice, 15-20 g, were injected with MA subcutaneously under various conditions. Mixed lymphocyte reaction (MLR) showed certain T cell subsets were affected by MA. The level of interleukin-2 (IL-2) production was inhibited due to a defect in expression of the IL-2 receptor. In mice injected with 20 mg MA/kg, 1 day before assay, phagocytosis of peritoneal macrophages showed $14.07\pm3%$, which was similar degree to 5 mg MA/kg treatment for 4 consecutive days. Phagocytosis was almost recovered to that of control after 4 day in 20 mg/kg injected mice. Maximum inhibition of plaque forming cell (PFC) occurred when MA was given early, indicating the inductive time point of antibody production was affected. The cortisol level increased in the MA treated group (0.05, 0.20, and $0.08{\mu}g$/dl for control, low, and high dose-MA treated mice, respectively). Based on these results, MA has general suppression effects on the immune systems by functional alteration of effector cells. Considering the increment of serum cortisol levels, MA partially impacts the neuroendocrine system to lead to failure of immune response.

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The Mucosal Immune System for the Development of New Generation Vaccine

  • Yuki, Yoshikazu;Kiyono, Hiroshi
    • 한국미생물생명공학회:학술대회논문집
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    • 한국미생물생명공학회 2003년도 2003 Annual Meeting, BioExhibition and International Symposium
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    • pp.55-62
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    • 2003
  • The mucosal immune system provides a first line of defense against invasion of infectious agents via inhalation, ingestion and sexual contact. For the induction of protective immunity at these invasion sites, one must consider the use of the CMIS, which interconnects inductive tissues, including PP and NALT, and effector tissues of the intestinal, respiratory and genitourinary tracts. In order for the CMIS to induce maximal protective mucosal immunity, co-administration of mucosal adjuvant or use of mucosal antigen delivery vehicle has been shown to be essential. When vaccine antigen is administered via oral or nasal route, antigen-specific Th 1 and Th2 cells, cytotoxic T lymphocytes(CTLs) and IgA B cell responses are effectively induced by the CMIS. In the early stages of induction of mucosal immune response, the uptake of orally or nasally administered antigens is achieved through a unique set of antigen-sampling cells, M cells located in follicle-associated epithelium(FAE) of inductive sites. After successful uptake, the antigens are immediately processed and presented by the underlying DCs for the generation of antigen-specific T cells and IgA committed B cells. These antigen-specific lymphocytes are then home to the distant mucosal effector tissues for the induction of antigen-specific humoral(e.g., IgA) and cell-mediated (e.g., CTL and Th1) immune responses in order to form the first line of defense. Elucidation of the molecular/cellular characteristics of the immunological sequence of mucosal immune response beginning from the antigen sampling and processing/presentation by M cells and mucosal DCs followed by the effector phase with antigen-specific lymphocytes will greatly facilitate the design of a new generation of effective mucosal antigen-specific lymphocytes will greatly facilitate the design of a new generation of a new generation of effective mucosal adjuvants and of a vaccine deliver vehicle that maximizes the use of the CMIS.

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블랙 알루미나의 연삭가공에 관한 연구 (Study on grinding of the black alumina)

  • 박종남;노승희;이동길
    • 한국산학기술학회논문지
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    • 제20권11호
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    • pp.7-12
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    • 2019
  • 반도체 시장에서 소재 개발 및 제조 공법에 대한 연구는 꾸준히 진행되고 있다. 일반적으로 자동 로봇용 End Effector는 알루미나(Al2O3)와 탄화규소(SiC) 등의 세라믹이 사용되었다. 본 연구는 대량생산이 가능한 분말 성형 프레스 법을 통해 반도체 현장에서 사용되는 블랙 알루미나를 개발하였다. 그리고 알루미나와 블랙 알루미나를 자동 로봇의 End Effector에 적용될 수 있도록 평면 연삭기를 사용하여 연삭가공을 실시하였다. 연삭가공을 통해 블랙 알루미나 대한 표면 거칠기(Ra)를 비교·분석하여 최적의 절삭 조건을 확인 할 수 있었다. 알루미나 표면 거칠기는 이송 속도가 0.72mm/sec이고 회전수가 1,700 rpm에서 0.4876 ㎛로 가장 양호하였다. 블랙 알루미나 표면 거칠기는 대부분의 절삭 조건에서 0.2 ㎛이하의 정밀도를 나타내었으며, 이송 속도가 0.72mm/sec이고 회전수가 1,900 rpm에서 0.1364 ㎛로 가장 양호하였다. 블랙 알루미나의 표면 거칠기는 알루미나 보다 0.35 ㎛ ~ 0.47 ㎛ 정도 양호하였다.

Anti-HER-2×anti-CD3 Bi-specific Antibodies Inhibit Growth of HCT-116 Colorectal Carcinoma Cells in Vitro and in Vivo

  • Ren, Hui;Li, Jun;Liu, Jing-Jing;Guo, Hui-Ling;Jiang, Tao
    • Asian Pacific Journal of Cancer Prevention
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    • 제13권6호
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    • pp.2795-2798
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    • 2012
  • Objective: This study is conducted to evaluate the effects of anti-HER-2${\times}$anti-CD3 bi-specific antibodies(BsAb) on HER-2/neuover-expressing human colorectal carcinoma cells. Methods: Growth was assessed by MTT assays after exposure of HCT-116 cells to Herceptin, anti-CD3 and BsAb antibodies. Immunocytochemistry was applied to test the HER-2 level of HCT-116. In a nude mouse model, HER-2${\times}$CD3 BsAb was combined with effector cells (peripheral blood lymph cells from normal human being) for observations on in Vivo growth of tumors. Results: Compared with the control group, using effector cells combined with anti-CD3 McAb, Herceptin or HER2${\times}$CD3 BsAb, tumor cell growth in vitro and in vivo was significantly inhibited (P<0.05), most remarkably in the HER2${\times}$CD3 BsAb case. The growth of xenografts with HER2${\times}$CD3 BsAb combined with effector cells was also significantly inhibited when compared with the anti-CD3 McAb or Herceptin groups (P<0.05). Conclusion: HER-2/neu might be a useful target for immunotherapy in colorectal carcinoma, anti-HER2${\times}$anti-CD3 BsAb exerting clear anti-tumor effects.

바이오 셀 조작용 지능 로봇 시스템 (An Intelligent Robotic Biological Cell Injection System)

  • 심재홍;조영임;김종형
    • 한국지능시스템학회논문지
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    • 제14권4호
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    • pp.411-417
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    • 2004
  • 최근 바이오 관련산업의 발전과 함께 바이오 장비 및 장치들에 대한 연구 및 개발이 활발하게 진행되고 있다. 특히 바이오 세포 조작관련 연구들이 많이 진행되어 오고 있다. 일반적으로 바이오 세포들에 대해 기계적인 엔드 이펙터들이 조작을 위해 접촉될 때 과도한 힘이 발생될 경우가 발생하며 이런 힘들에 의해 세포막이나 조직들이 피해를 입을 수 있다. 본 논문에서는 상기 문제들을 극복하기 위해 바이오 세포 조작을 위한 새로운 시스템을 제안하였다. 제안된 시스템은 내장된 힘 센서를 이용하여 바이오 세포와 엔드 이펙터간의 발생 힘을 측정할 수 있다. 또한, 비전기술을 이용하여 엔드 이펙터의 피펫 팀을 바이오 세포막까지 정확하게 가이드 할 수 있다. 결과적으로 제안된 시스템은 바이오 세포에 피해를 주지 않고 안전하게 조작이 가능하다. 제안된 기술을 이용하여 실제 시작품을 제작하여 다양한 실험을 수행한 결과 향후 DNA 조작과 같은 바이오 세포 조작용 정밀 인젝션 시스템으로의 사용 가능성을 보여 주었다.

PHC 파일 두부정리 자동화 장비의 말단장치 개발 (Development of the End-effector for Developing a PHC Pile Cutting and Crushing Machine)

  • 이정호;김영석;조문영;김성근;성낙원
    • 한국건설관리학회:학술대회논문집
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    • 한국건설관리학회 2004년도 제5회 정기학술발표대회 논문집
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    • pp.531-534
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    • 2004
  • 재래식 두부정리 작업은 노동 집약적이며 노무자간의 숙련도 차이에 의해 품질 및 작업 생산성이 크게 영향을 받고 있다. 국내 $\cdot$ 외에서는 두부정리 작업의 생산성 및 안전성, 품질을 향상시키기 위해 자동화 장비를 개발 중에 있으나 기존에 개발된 두부정리 자동화 장비는 파일 파쇄 작업만을 자동화 대상으로 하고 있고, PHC 파일에 종방향 균열을 발생시켜 두부정리 작업의 품질을 크게 저하시키고 있는 실정이었다. 기존 두부정리 자동화 장비가 PHC 파일에 종방향 균열을 발생시키는 원인은 PHC 파일의 물리적 특성을 고려한 자동화 장비 말단장치의 설계 및 제작, 배치가 제대로 이루어지지 못한 것으로 분석되었다. 따라서, 본 연구에서는 기존에 개발된 두부정리 자동화 장비 및 본 연구를 통해 현재까지 개발된 두부정리 자동화 장비 파일롯타입의 실험결과를 토대로 PHC 파일을 종방향 균열 없이 효과적으로 파쇄할 수 있는 두부정리 자동화 장비 프로토타입의 말단장치를 개발하고자 한다.

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